INFLUENCE OF DONOR AND RECIPIENT GENOTYPES ON CYP2D6 PHENOTYPE AFTER LIVER-TRANSPLANTATION - A STUDY OF MUTATIONS CYP2D6(ASTERISK)3 AND CYP2D6(ASTERISK)4

Objective: After liver transplantation (LT), genotypic differences bet ween the recipient and the transplanted liver, medications and post-LT complications may all affect drug metabolism. We have studied the eff ect of two CYP2D6 mutations in the donor and the recipient on post-LT CYP2D6 phenotype. Method: The CYP2D6 phenotype was assessed in 48 pati ents before and after LT with debrisoquine or dextromethorphan. CYP2D6 3 (CYP2D6A) and CYP2D6*4 (CYP2D6B) mutations were detected in the don or and the recipient using polymerase chain reaction. Results: Before LT, 40 subjects were classified as extensive metabolisers (EM) and 8 a s poor metabolisers (PM); after transplantation, 41 were EMs and 7 wer e PMs. Genotype and phenotype were in agreement in 100% of EMs and 40% of PMs. The low percentage of agreement in PMs could not be explained by severely altered liver function. The phenotype of 13 subjects was apparently changed by LT: 6 EMs became PMs and 7 PMs became EMs. All f our subjects in whom genotype changed following LT had a corresponding change in phenotype: two EM subjects became PMs and two PM subjects b ecame EMs. Conclusion: The low percentage of agreement in PMs may be p artly explained by mutations other than CYP2D63 and CYP2D6*4. Neverth eless, our study shows that the CYP2D6 genotype of the donor controls the phenotype of the recipient of a liver transplantation.